CN110198720A - Compositions and methods for treating herpes viruses in mammals - Google Patents

Abstract

Compositions and methods for ocular infections are disclosed, the methods comprising treating ocular herpes virus infections, including Feline Herpes Virus (FHV), Canine Herpes Virus (CHV), and Equine Herpes Virus (EHV), wherein the compositions comprise povidone-iodine and DMSO.

Description

For treating the composition and method of the herpesviral in mammal

Background of invention

The present invention relates to treatment method, the virus including eye surface and periocular area for treating non-human mammal The stable topical formulations of infection.The invention further relates to the scheroma and eye surface function barrier for treating non-human mammal The method hindered.

Feline herpetovirus (FHV), and particularly 1 type of FHV (FHV-1), are a kind of virus highly infectious, are cats One of the main reason for infection of the upper respiratory tract (URI) or cat influenza.In addition, FHV has described as the diseases of eye surface of cat, it is all Such as the most common viral reason of feline herpesvirus keratitis.Feline herpetovirus I (FHV-1) be feline viral rhinotracheitis (FVR), The Causative virus of the infection of the upper respiratory tract and related diseases toxicity ocular infection.It has keeps latence to make infection in eyes Recurrence (reoccurrence) (or recurrence (recrudescence)) becomes common ability.80% cat is in primary infection Become carrier afterwards, and the cat of vaccine inoculation is likely to become chronic carriers, without the evidence of clinical disease.Recurrence may With pressure, operation, lactation, corticosteroid therapies and by feline leukaemia virus (FeLV) or feline immunodeficiency virus (FIV) Immunosupress caused by infecting is related.

FHV-1 is easy to propagate in the epithelium of respiratory tract and conjunctiva.The course of infection of conjunctival epithelium is self limiting.Epithelium Damage in two days after infection is it will be evident that and being most apparent in seven days to ten days.Intranuclear inclusion be easy by It influences to identify in the Histological section of tissue, but is less susceptible to identify in the cytolgical examination of conjunctiva scrape.

Acute FHV-1 infection usually occurs in newborn and young adult cat.Upper airway symptoms to sneeze and Based on nose and discharge of eye.Eye symptom includes bilateral conjunctivitis, is likely to become mucus shape or mucopurulent serosity eye Secretion and blepharospasm.Keratopathy is less obvious during acute primary FHV-1 infects.After infection 3 days and 6 days it Between it can be seen that micro- dendron shape lesion.In new wave virion after the release of the conjunctiva of degeneration, the about the 11st day it can be seen that more Big dendron.These lesions are very subtle, and only dendron can merge to form bigger geographical lesion (geographic once in a while lesion).Corneal infection leads to relatively small cytopathic effect at this stage, without inflammatory reaction.It is likely to occur slight Of short duration superficial vein.

Virus lays dormant is exactly to establish at this stage.The reactivation of latent virus results in the recurrence seen in geriatric cat Infection.Recurrent infection usually occurs in adult cat, these adult cats are probably just from primary FHV-1 early stage life Restore in infection.In adult cat, the FHV-1 infection of recurrence may only result in conjunctivitis, or may also lead to keratitis.On Respiratory symptom there is usually no.Conjunctiva form is usually made of slight conjunctival congestion and intermittent discharge of eye.Process may Extend, and often recurs.

If corneal involvement, vital stain such as rose-bengal is can be used to observe in dendron columnar epithelium lesion.Dendron Often merge and forms geographic " map shape " lesion.Then it is often lighter substrate oedema and superficial stromal vascular.Bleb Property keratitis matrix be involved by very big concern because being likely to occur apparent matrix scar.This form is characterized in that Corneal edema, deep-level blood vessel, inflammatory cell infiltration and the damage of final collagen and muddiness.Think, the matrix of FHV-1 keratitis Form not instead of virus directly affects keratocyte, the disease to viral antigen mediated by cytotoxic T lymphocyte Reason immune response.

The complication of herpetic keratitis includes keratoconjunctivitis sicca (dry eyes), (conjunctiva is viscous to cornea for atretoblepharia It is attached) and corneal necrosis.KCS may be caused due to dacryoadenitis or it may be the tubule due to the cat with FHV-1 conjunctivitis Caused by obstruction.When inflammatory resolution, drying property tends to subside.Atretoblepharia is likely to occur in conjunctival epithelium and there is obvious damage From anywhere in, and be therefore likely to occur in after FHV-1 conjunctivitis.Cat corneal necrosis (Feline sequestrum) can Can occur corneal stroma there are chronic injury or stimulation whenever, and be likely to occur in after FHV-1 keratitis.

Result of the diagnosis of FHV-1 ocular infection based on clinical medical history, the discovery of clinical examination and appropriate diagnostic test.Angle Film dendron may be very subtle, and it is necessary to use rose-bengal, a kind of vital stain detecting them.Due to through thickness Epithelial erosion usually occurs over just in terminal illness, therefore fluorescent staining may not be helpful.For many years, virus purification It is the most sensitive means to feline herpetovirus eye disease progress positive diagnosis, but largely by polymerase chain Formula reacts (PCR) test replacement.Business collection virus swab is soaked with transport medium (transport medium), and is rolled up Enter conjunctival cul-de-sac.Then swab is put into transport medium and submits to laboratory.

Conjunctivo-cytology is not the reliable method for diagnosing FHV-1 eye disease.Intranuclear inclusion is easy in affected tissue Histological section in see, conjunctiva apply on piece it is usually unobvious.The presence of the distinctive intracytoplasmic inclusion of choamydiae infection It is become apparent from the Giemsa dyeing of conjunctiva smear.Therefore conjunctivo-cytology is valuable in terms of excluding chlamydial conjunctivitis. Chlamydia, mycoplasma or calicivirus ocular infection cause keratopathy to be uncommon.

When there are the upper respiratory tracts by for a long time, the treatment to the acute FHV-1 infection of young cat includes that whole body is given and part is applied The broad-spectrum antibiotic added.Impaired newborn may need generally to support, and this may include making for liquid, heat and evaporator With.If there is corneal involvement, then place's topical antiviral drug is opened.In the adult cat with recurrent FHV-1 infection, part Antiviral drugs preferably uses early stage lysis, before matrix involvement progress aggressively.

In eye disease similar with feline herpetovirus -1 (FHV-1) progress, canine alphaherpesvirus -1 or CHV-1 can feel Contaminate eye mucous membranes, conjunctiva and the cornea of canid.CHV-1 is classified as α herpesviral, has Herpesvirus (Herpesviridae) many features including short replicative cycle, induce lifelong incubation period and narrow host range.CHV-1 exists Especially concerned in puppy, in puppy, virus can cause lethal hemorrhage to infect, and lead to local organs necrosis and death. In adult dogs, infection is usually asymptomatic, but can show as the infection of the upper respiratory tract and eye disease.

The ocular infection as caused by CHV-1 is only just described recently in dog.CHV-1 can be present in many ways In mature dog, both ocular adnexa and eye surface are influenced.These performance include blepharitis, conjunctivitis, ulcerative keratitis and it is non-burst Ulcer keratitis.These situations can develop during the primary of CHV-1 and/or recurrent infection.Due to other blebs The relationship of Tobamovirus, it is believed that its natural history and epidemiology is similar to FHV-1.

In the eye disease progress similar with FHV/CH, horse herpes virus -1 and horse herpes virus -2 have involved and have drawn Play the eye disease of horse.There are the various serotypes of horse herpes virus, and most of cause to fall ill outside eyes.EHV-2 is returned Class is gamma herpes viruses, it is different from other viruses in herpetoviridae, because its proliferative speed is than other subfamilies member It is more volatile.EHV-2 has been involved in the keratoconjunctivitis including epidemic disease type, conjunctivitis and keratitis.EHV-1 is Be involved in in multifocal choroidoretinitis, it has been speculated that, multifocal choroidoretinitis after viremia virusemia through by The injury of blood vessel of eyes occurs.Due to the relationship with other Herpesvirus, it is believed that the natural history and epidemiology of EHV-1 with FHV/CHV is similar.About EHV-2 and gammaviridae, the mode and rate of duplication may be more closely similar to its of the subfamily He is member.

EHV-2 and Gammaviridae is a viral subfamily in herpetoviridae.In latter subfamily at present There are 32 species, and wherein mammal is as natural host.These viruses are due to via epstein-Barr virus or card wave The relevant herpesviral of Ji sarcoma causes certain infection the most significant in the mankind.Therefore, Gammaviridae can drench It is replicated in bar cell, fibroblast or epithelial cell and continues to exist.Horse herpes virus -2 or EHV-2 are also sorted in bleb In Tobamovirus (genus Rhadinovirus), it is known that slow including duplication in eye mucous membranes and lymph node in horse tissue.It Replicative cycle is similar with other herpesvirals, because it is core and lysogenicity.Herpesviral also as they from its host Cytogene is stolen in cell and the ability being integrated into its genome is unique.Cyclin gene be exactly one this The example of sample, it adjusts cell division, and may cause carcinogenic phenomenon.

Three kinds of antiviral drugs are available.Iodoxuridine (IDU) is by replacing required nucleotide thymidine viral interference DNA to close At.IDU poorly soluble, and be to inhibit virus.It needs to contact for a long time with the tissue of infection.0.1% solution must be daily It is applied five times.IDU is as Stoxil (Smith Kline&French) and Herplex (Allergan Pharmaceuticals it) sells.Spongoadenosine inhibits viral dna polymerase, and therefore reduces viral DNA and close At.It sells as Vira A (Parke Davis), and 3% ointment is applied five times daily.Trifluorothymidine incorporation virus In DNA and lead to the synthesis of deficient protein.It is sold as Viroptic (Burroughs Wellcome), it is considered as most Effectively, the minimum and most soluble antiviral drugs of toxicity.It is also most expensive.It is available as 1% solution, when animal is awake When, every two hours apply Viroptic, until cornea re-epithelialization, then reduces to awake and, up to every four hours, continue another Outer two weeks.Acyclovir is to can be used for the newest antiviral drugs of nerpes vinrus hominis.It is a kind of oral piece given Agent, and with trade name Zovirax (Burroughs Wellcome) sale.The research of Nasisse indicates that trifluorothymidine is to cat Herpesviral is most effective, followed by iodoxuridine, followed by spongoadenosine.Although acyclovir is to human simple blister Exanthema virus is most effective, but invalid to feline herpetovirus.This may be since FHV-1 not can induce deoxycytidine kinase.

The adjuvant treatment herpetic keratitis in recent years reported other strategy include locally apply interferon, L- lysine is administered orally and Cimetidine is administered orally.It is reported that local immunity of the interferon stimulation to virus infection.Manually 20Iu/ml-50IU/ml solution in tear is applied topically twice daily.It is reported that the L-lysine being administered orally passes through Reverse transcriptase inhibits the growth of herpesviral to arginic intake needed for virus multiplication.It is daily with the dosage of 125mg It is given twice to cat.Cimetidine, which has been shown, usually stimulates cell-mediated be immunized.It is given once a day with the dosage of 50mg. In the streets report shows that cat maintains one of these drugs or more during quiescent time section, before will lead to infection and recurrence There is longer time section, and when recurring generation, infection is relatively light and the duration is shorter.

If careful use and be used in combination with antivirotic, corticosteroid can be used for treating chronic herpetic stromal Keratitis is to inhibit potential scar to be immunoreacted.If epithelium or conjunctiva involvement are still active, steroids is disabled, because of class Sterol can postpone re-epithelialization, extend virus shedding, and conjunctiva and corneal epithelium may be allowed to infect and involve corneal stroma.It can Selectively, careful using local cyclosporin, to reduce scar relevant to herpesviral stromal keratitis.

Certain antiviral drugs are currently used for treatment eye FHV, CHV or EHV infection, but they are unfavorable, because it Be usually expensive drug, need frequent part to apply or have undesirable side effect.In addition, most of current therapies The support for the In vivo study not all being well controlled, the clinical application that these researchs demonstrate them is reasonable.For example, Clinically it is usually used in treating the anti-bleb nucleoside analog of the herpes ophthalmicus virus infection of cat, cidofovir and acyclovir, Previously assessed in traditional external two-dimentional cat cell culture.Cidofovir is also in dog In vivo model It is assessed, and shows and reduce virus shedding, but topical ophthalmic toxicity is significant.

Therefore, it is necessary to the novel therapeutic choice for treating eye FHV, CHV or EHV infection, these therapeutic choices are Effectively, cost-effective, and without the need for frequent application.

Summary of the invention

The present invention uses the combination of penetration enhancers and disinfectant (antiseptic) ingredient, to deliver effective therapeutic agent The drug of amount, the non-limiting example member including iodophor agent disinfectant classification, wherein dimethyl sulfoxide is used as infiltration enhancing Agent.The periocualr skin of a variety of non-human mammals and the infection of eye surface are treated using the composition.Such strategy Ideal because it allow poly- antimicrobial via safe and convenient approach with effective, nontoxic concentration in non-human The skin of periocular area is quickly and efficiently delivered in mammal and across the dermal delivery of periocular area and across angle Film, conjunctiva and the delivering of other eye surface structures.

In one embodiment, disclosed herein is the composition for treating eye feline herpetovirus (FHV) infection, institutes Stating eye feline herpetovirus (FHV) includes 1 type of FHV (FHV-1).As used herein, term " feline herpetovirus " and " FHV " It is interchangeably used, and covers all types of feline herpetovirus, including felid herpesvirus 1 type (FHV-1).Group of the invention Closing object includes povidon iodine (PVP-I) and dimethyl sulfoxide (DMSO), and wherein the composition is without using valuableness It is effective to treatment FHV infection in the case where nucleoside analog antiviral drug.

In one embodiment, the composition disclosed herein for treating FHV infection is substantially anhydrous.One In a embodiment, composition is anhydrous.

In one embodiment, it is disclosed herein for treat FHV infection composition include 0.01% to less than The PVP-I of 0.5% (w/w).In one embodiment, PVP-I is to be selected from by about 0.05% to about 0.4%, about 0.1% to about 0.3%, the range of the group of about 0.2% to about 0.275% composition exists.In one embodiment, PVP-I is selected from by about 0.1%, the amount of the group of about 0.15%, about 0.2%, about 0.25%, about 0.3%, about 0.35%, about 0.4%, about 0.45% composition In the presence of.Preferably, composition of the invention includes about 0.25%PVP-I.

In one embodiment, the composition disclosed herein for treating FHV infection also includes that at least one is selected from The antifungal agent for the group being made up of: Tolnaftate, Terbinafine, undecenoic acid, clioquinol, Miconazole, nitric acid miaow health Azoles, clotrimazole (clorrinazole), tioconazole, nystatin, terconazole (terconazoic), Butoconazole Nitrate, Ciclopirox Amine, econazole nitrate, triacetin, Flucytosine, Haloprogin and ketoconazole.In one embodiment, antifungal agent is with about The amount of 1% to about 25% (w/w) exists.

In one embodiment, disclosed herein is a kind of method for treating FHV, CHV or EHV infection, the sides Method includes contacting the anterior corneal surface of infection with compositions disclosed herein, and repeat contact procedure as needed, until FHV, CHV or EHV infection are treated.In one embodiment, contact procedure carries out at least once daily.In an embodiment party In case, contact procedure carries out at least twice daily.

In one embodiment, disclosed herein is a kind of method for treating FHV, CHV or EHV infection, the sides Method includes contacting the anterior corneal surface of infection with compositions disclosed herein, and repeat contact procedure for about three days to about two The period in week.In one embodiment, contact procedure was repeated for about one week.

Detailed description

The present invention relates to containing dimethyl sulfoxide (DMSO)/povidone iodine (PVP-I) composition in non-human lactation The method of eye surface and periocualr skin local treatment is carried out in animal.Surprisingly, the present invention can be used for treating virus, fungi And bacterium infection.

Cause the specific but non-limiting example of the preparation for the useful pharmaceutical preparation that can be used in the method by molten Solve or be suspended in the solid PVP-I composition in DMSO.Said preparation can be used for treating feline herpesvirus keratitis and cat conjunctivitis.

In one embodiment, composition includes the iodophor in the range of about 0.01% to about 15%.Another In a embodiment, composition includes the iodophor between 0.05% and 12.5%.In another embodiment In, composition includes the iodophor between 0.05% and 10.0%.In another embodiment, composition packet The iodophor being contained between 0.1% and 10.0%.In another embodiment, composition is included in 0.1% He Iodophor between 5.0%.In another embodiment, composition includes between 0.25% and 9.0% Iodophor in range.In another embodiment, composition includes that the iodine between 0.2% and 2.5% carries Body.

In another embodiment, composition includes the iodophor between 0.5% and 7.5%.Another In one embodiment, composition includes the iodophor between 0.5% and 1.0%.In another embodiment In, composition includes the iodophor between 0.75% and 5.0%, and again in another embodiment Iodophor between 1.0% and 4.0%.In one embodiment, composition is included in about 0.1% to about 2.5%, the iodophor in about 0.2% to about 2.0%, about 0.3% to about 1.0% and about 0.4% to about 0.75% range.

In another embodiment, DMSO may be added in the aqueous solution of PVP-I.In an example, DMSO can exist with water in the range of 10%-99% as cosolvent.One embodiment of such preparation can be with Including a series of excipient, such as sodium chloride, biphosphate sodium-hydrate, Anhydrous Disodium Phosphate and water and this field Other excipient known to technical staff.

Povidone iodine (PVP-I) is disinfectant (antiseptic) known to a kind of nearly all medical speciality.Its conduct The therapy of active infections for eyes, ear, nasal sinus, joint chamber and skin has been obtained for surmounting simple disinfection recently Interest.The percutaneous absorbtion of known a variety of organic solvents enhancing drug including dimethyl sulfoxide (DMSO).However, in inventor Before the discovery of oneself, it is not known that DMSO can be used as the penetration enhancers of big (high molecular weight) polymerizable compound such as PVP-I.Cause This, actually avoids and uses DMSO as solvent for therapeutic preparation in the composition comprising PVP-I.

In an aspect, as further described herein, in fact it has surprisingly been found that (be less than comprising relative lower concentration PVP-I 0.5%w/w) and it is greater than 30%, preferably 30%-75%, more preferably 30% to 45% and most preferably about The composition of 44% DMSO infects the FHV for the treatment of anterior corneal surface effective.This is favourable, and is surprising, portion Point be because commonly known is stimulant when PVP-I is applied directly to anterior corneal surface, and can cause inflammation, it is rubescent and Burning sensation.The PVP-I of relatively low-dose, all such as less than 5%, and preferably about 0.25%PVP-I, can be it is highly effective, Without causing stimulation, rubescent or calcination.

In another aspect, as further described herein, in fact it has surprisingly been found that the composition covered herein and side Method can be used for treating the eye disease in addition to FHV infection, including but not limited to fungal infection, yeast infection, other virus senses Dye and bacterium infection, including the bacterium infection as caused by the gram-positive bacterium and gramnegative bacterium in eyes.Therefore, It can also include at least one other antimicrobial according to the composition that title is invented (in addition to PVP-I).For example, title The composition of invention may include at least one other antifungal agent for treating fungal infection, at least one for treating The other anti-yeast agent of yeast infection, at least one other antivirotic for treating other virus infections or at least It is a kind of for treating the other antibacterial agent of bacterial-infection resisting.

It is contemplated herein that be for treat the eye FHV in animal infection composition, the composition include at least one For the solvent of bleeding agent and at least 0.1%, preferably about 0.25% PVP-I.Animal can advantageously be felid, such as Domestic cat, but may include the animals such as Canidae, equine, pig, and treat animal in need for the treatment of using composition of the invention Herpes ophthalmicus virus infection method.

In one embodiment, disclosed herein is the compositions of the DMSO comprising > 30% and the PVP-I less than 0.5%. Composition of the invention preferably includes the PVP-I being completely dissolved in a solvent.In a preferred embodiment, composition In do not exist as the solid or undissolved PVP-I of particle or suspended matter.

There is disclosed herein the methods for using described PVP-I/DMSO composition.Composition of the invention may include Cosolvent.Cosolvent can be water or aqueous cosolvent, or can be absolute alcohol or anhydrous organic cosolvent.Cosolvent can be with It is ethylene glycol or polyethylene glycol.Composition can be free of ethylene glycol or can be free of polyethylene glycol.

In addition, composition may include can provide the gelling agent of adhesion properties for composition so that composition be gel, Ointment, emulsifiable paste or ointment, the composition is in effect, acceptable residence time and storage properties at the position for applying or using Purpose on be stable, such as with pharmaceutically acceptable storage life.Be not present gelling agent in the case where have phase Liquid composition compared with low viscosity is compared, the relatively highly viscous composition comprising gelling agent is for extending composition Period in be located in eye surface and can be advantageous.For example, being applied to the liquid composition of eye surface can pass through Less than one hour, usually less than half an hour after initial application, and usually sheds tears and be flushed away in -15 minutes 10 minutes. Gel combination can be continued above 15 minutes, usually more than half an hour in eye surface, and preferably no more than at least One hour and be greater than one hour.

Gel composition for eyes of the invention may include as known in the art selected from natural gum, agar, carragheen, all scholars The gelling agent of woods or cellulosic polymer etc..A kind of preferred cellulosic polymer that can be used as gelling agent is hydroxyethyl cellulose (HEC).Selectable cellulosic polymer gelling agent is hydroxymethyl cellulose (HMC) or hydroxypropyl methyl cellulose (HPMC).

Composition of the invention preferably includes povidone iodine or PVP-I with the average molecular weight greater than 10,000. It is highly preferred that composition of the invention includes the PVP- with the average molecular weight between about 20,000 to about 1,000,000 I.One preferred embodiment includes with the average mark between about 30,000 to about 60,000 or higher average molecular weight The PVP-I of son amount.Every kind of PVP-I ingredient is referred to herein as " high molecular weight PVP-I " or " HMW PVP-I ".

Another embodiment of composition according to the present invention is stable local eye-gel preparation, and it includes about The povidone iodine (PVP-I) of 0.1% to about 10%；The dimethyl sulfoxide (DMSO) of about 30% to about 99%；About 1% to about 10% gelling agent；Wherein, every kind of ingredient in composition is acceptable on ophthalmology, and with substantially free of gelling agent simultaneously And include that the povidone iodine of about 0.1% to about 10% is compared with the liquid composition of the DMSO of about 30% to about 99%, this is ophthalmically acceptable Gel combination shows bigger effect in terms of the infectious situation for the treatment of eyes or eyelid.

Preferred gel composition for eyes includes about 0.5% to about 5%PVP-I.Preferred gel composition for eyes packet Containing about 1% to about 3%PVP-I, and most preferred gel composition for eyes includes about 1%PVP-I.

Composition of the invention preferably includes povidone iodine or PVP-I with the average molecular weight greater than 10,000. It is highly preferred that composition of the invention includes the PVP- with the average molecular weight between about 20,000 to about 1,000,000 I.One preferred embodiment includes high molecular weight (HMW) PVP-I.

Preferred gel composition for eyes includes the DMSO of about 30% to about 70%.Preferred gel composition for eyes can With the DMSO comprising about 40% to about 49%, and even more preferably about 44% DMSO.

Preferred gel composition for eyes includes the gelling agent of about 0.25% to about 5%.Preferred gel for eye use combination Object may include the gelling agent of about 0.5%-3.5%.What is be produced is used to treat the particularly useful of the infection of eyes or eyelid Composition includes 1%PVP-I；44%DMSO；With 1%-3% hydroxyethyl cellulose (HEC)；With equilibrium water property solvent and other Inactive excipient.Preferred aqueous solvent is water or isotonic buffer solution.

Treat indication

In one embodiment, disclosed herein is the compositions and method of the FHV infection for treating eye surface.Cause This, composition and method can be used for treating eyes or ocular surface, such as cornea and neighbouring or contact eye surface region, Such as eyelid.Composition and method can also be used to treat any of the above combination.

As used herein, term " treatment " refers to disclosing or covering with present disclosure in the eye surface of mammal Composition contact after, the mitigation of the symptom of the improvement and/or situation of detectable deleterious situation.It is unfavorable that term " treatment " is covered The part of situation improves and the complete elimination (that is, " healing ") of situation the two.In an aspect, treatment infection.

Composition and method can be used for treating the infection that including but not limited to virus infection includes feline herpetovirus (FHV).

Composition and method can be used for treating at least two one kind or any in disease above, situation or pathogen Combination.

Composition

In one embodiment, composition includes at least one therapeutic agent and at least one solvent and/or bleeding agent.? In one aspect, iodophor is therapeutic agent.In one embodiment, composition includes at least one disinfection compound.One In a aspect, disinfection compound is therapeutic agent.In one embodiment, composition includes iodophor disinfectant.As made herein " iodophor " refers to the substance comprising iodine and at least one other agent (such as solubilizer), in the solution release trip From iodine.The example of iodophor includes but is not limited to povidone iodine (PVP-I), the tincture of iodine, Shandong Ge Shi solution (Lugol ' ssolution) With salt compounded of iodine (such as potassium iodide, sodium iodide).

In one embodiment, composition includes at least one iodophor.Composition covers any iodophor, Yi Jishang The iodophor do not developed or found.In one embodiment, iodophor is PVP-I.In another embodiment, it combines Object includes iodine.In one embodiment, composition includes iodine and at least one iodophor.In one embodiment, it combines Object includes PVP-I and DMSO, and without other or supplement iodophor and elemental iodine.

In one embodiment, PVP-I is used as active constituent or therapeutic agent to work in the composition.In one aspect In, PVP-I therapeutic agent works as disinfectant.In another embodiment, PVP-I rises as preservative in the composition Effect.In another aspect, PVP-I preservative works as stabilizer.In one embodiment, PVP-I is being combined It is worked in object at least one ability.In another embodiment, PVP-I is acted as in the composition at least two abilities With.In another embodiment, composition of the invention can be free of other preservative or stabilizer.

In another embodiment, composition also includes at least one non-iodophor, non-iodine therapeutic agent.Implement at one In scheme, at least one non-iodophor, non-iodine therapeutic agent are disinfectants.In another embodiment, at least one non-iodine carries Body, non-iodine therapeutic agent are not disinfectants.In one embodiment, composition of the invention may include PVP-I and DMSO, and And be free of non-iodophor disinfectant and non-iodine vehicle treatment agent.

In one embodiment, at least one non-iodophor, non-iodine therapeutic agent are antifungal agents.Suitable antifungal agent Including such as allylamine and azole.In one embodiment, antifungal agent includes but is not limited to Tolnaftate, Terbinafine, ten One carbon enoic acid, clioquinol, Miconazole, miconazole nitrate, clotrimazole (clorrinazole), tioconazole, nystatin, Te Kang Azoles (terconazoic), Butoconazole Nitrate, Ciclopirox Olamine, econazole nitrate, triacetin, Flucytosine, Haloprogin and ketone health Azoles.In one embodiment, composition of the invention may include PVP-I and DMSO, and antimycotic without non-iodophor Agent.

In one embodiment, composition includes one or more of physical therapy (naturopathic) substances.Physical therapy object Matter includes but is not limited to pomegranate (Punica Granatum) (pomegranate (Pomegranate)) extract, tea tree (Camellia Sinensis) leaf (green tea (Green Tea)) extract, ascorbic acid (vitamin-C), pot marigold (Calendula Officinalis) extract, glycyrrhiza glabra (Glycrrhiza Glabra) (Radix Glycyrrhizae (Licorice)) extract, allantoin and Cucumber (Cucumis Sativus) (cucumber (Cucumber)) fruit extract.

In one embodiment, composition includes DMSO, PVP-I, pomegranate (Punica Granatum) (pomegranate (Pomegranate)) extract, tea tree (Camellia Sinensis) leaf (green tea (Green Tea)) extract, Vitamin C Acid (vitamin-C), pot marigold (Calendula Officinalis) extract, glycyrrhiza glabra (Glycrrhiza Glabra) (Radix Glycyrrhizae (Licorice)) extract, allantoin and cucumber (Cucumis Sativus) (cucumber (Cucumber)) fruit extract Object.In one embodiment, composition of the invention includes PVP-I and DMSO, and is free of physical therapy agent.

In one embodiment, composition includes at least one solvent and/or bleeding agent.In one embodiment, One-component can work as both solvent and bleeding agent in the composition.In one embodiment, composition includes DMSO.In an aspect, DMSO works as the bleeding agent of active component.In an aspect, DMSO rises as solvent Effect.In yet other aspects, DMSO works as both solvent and bleeding agent.In one embodiment, DMSO is Unique bleeding agent in composition.In one embodiment, DMSO is unique solvent in composition.In an embodiment In, DMSO is unique bleeding agent and solvent in composition.

In one embodiment, composition includes PVP-I and DMSO.In another embodiment, composition by PVP-I and DMSO composition.In another embodiment again, composition is substantially made of PVP-I and DMSO.Implement at one In scheme, composition includes PVP-I and DMSO and cosolvent.In one embodiment, composition include PVP-I, DMSO, Cosolvent and gelling agent.In one embodiment, composition is made of PVP-I and DMSO and cosolvent.Implement at one In scheme, composition is made of PVP-I, DMSO, cosolvent and gelling agent.Above-described composition it is any in, group Second therapeutic agent or the second active constituent can be free of by closing object.Above-described composition it is any in, composition can be with Without in the composition as particle or the solid or undissolved ingredient of suspended matter.

Based on this disclosure, it will be appreciated by those skilled in the art that how to identify to the composition and side covered herein The useful bleeding agent of method.In one embodiment, bleeding agent is a kind of increasing that can be used for making composition infiltration mucus or skin The bleeding agent of thick-layer, no matter the thickening layer be nature dissection a part or as caused by the infection treated.As non-limit Property example processed, methyl sulfonyl methane may be used as such as the bleeding agent in the composition covered herein.

In one embodiment, composition includes at least one cosolvent.In one embodiment, composition includes As the DMSO of primary solvent, and also comprising at least one cosolvent.In one embodiment, water is cosolvent.One In a embodiment, composition includes the DMSO as primary solvent and the water as cosolvent.In one embodiment, group Object is closed to be made of the DMSO as primary solvent and the water as cosolvent.In another embodiment, composition is substantially It is made of the DMSO as primary solvent and the water as cosolvent.In one embodiment, composition includes at least one Cosolvent, such as, but not limited to water or ethyl alcohol.In one embodiment, cosolvent is that one or more of aprotic, polars are molten Agent.In one embodiment, cosolvent is ethyl acetate.In one embodiment, cosolvent be ethyl acetate, acetone, At least one of acetonitrile, tetrahydrofuran, methylene chloride and dimethylformamide.The example of cosolvent includes but is not limited to alcohol (alcohol), silicone, polyethylene glycol, ethylene glycol and combinations thereof.In one embodiment, cosolvent is diethylene glycol list second Ether (DGMEE).In one embodiment, cosolvent is propylene glycol.

In view of disclosure set forth herein, those skilled in the art are by property and object based on such potential cosolvent It manages effect and understands the advantages of using cosolvent and limitation.

In one embodiment, composition includes iodophor and bleeding agent, and includes also water, and wherein water content is about At least 0.01%, about at least 0.02%, about at least 0.03%, about at least 0.04%, about at least 0.05%, about at least 0.06%, About at least 0.07%, about at least 0.08%, about at least 0.09%, about at least 0.1%, about at least 0.2%, about at least 0.3%, about At least 0.4%, about at least 0.5%, about at least 0.6%, about at least 0.7%, about at least 0.8%, about at least 0.9%, about at least 1.0%, about at least 1.5%, about at least 2.0%, about at least 2.5%, about at least 5%, about at least 7.5%, about at least 10%, about At least 12.5% or bigger.In one embodiment, composition includes iodophor and bleeding agent, and also includes water, wherein Water content is to be approximately less than 0.01%, be approximately less than 0.02%, be approximately less than 0.03%, be approximately less than 0.04%, be approximately less than 0.05%, be about small In 0.06%, it is approximately less than 0.07%, is approximately less than 0.08%, is approximately less than 0.09%, is approximately less than 0.1%, is approximately less than 0.2%, about small In 0.3%, it is approximately less than 0.4%, is approximately less than 0.5%, is approximately less than 0.6%, is approximately less than 0.7%, is approximately less than 0.8%, is approximately less than 0.9%, be approximately less than 1.0%, be approximately less than 1.5%, being approximately less than 2.0%, being approximately less than 2.5%, being approximately less than 5%, being approximately less than 7.5%, It is approximately less than 10%, is approximately less than 12.5% or bigger.In one embodiment, composition includes iodophor and bleeding agent, and Also include water, wherein water content be about 0.01% to about 12.5%, about 0.02% to about 10.0%, about 0.03% to about 7.5%, About 0.04% to about 5%, about 0.05% to about 2.5%, about 0.06% to about 2%, about 0.07% to about 1.5%, about 0.08% To about l%, about 0.09% to about 0.9%, about 0.1% to about 0.8% or about 0.2% to about 0.7%.In an aspect, water The component of composition can be derived from.In another aspect, water can be particularly added to composition.

In one embodiment, composition includes at least one excipient, such as, but not limited to sodium chloride, biphosphate Sodium-hydrate, Anhydrous Disodium Phosphate and water.The composition covered herein will be understood as optionally comprising one or more Kind other excipient well known by persons skilled in the art.Those skilled in the art will know how to identify such excipient at this It is useful in the composition and method of invention, for example, when the therapeutic effect of such excipient enhancing composition or method, steady When qualitative or effect.

Dosage, form and preparation

In one embodiment, composition includes at least one therapeutic agent of therapeutically effective amount.Unless otherwise directed, no Then term " therapeutically effective amount " is herein for describing in the environment for generating or realizing the chemical combination of expected treatment results The amount of object.In one embodiment, it is contemplated that treatment results be related to the treatment of onychomycosis.In one embodiment, it controls Treating effective quantity is to be enough to treat the amount that FHV infects, and the treatment of FHV infection includes prevention or slows down the progress of infection, prevents At least some infection and elimination all at least one of infection are eradicated in the diffusion of infection.

In an aspect, therapeutically effective amount can be determined based on single dosage, or can be based on the more of composition A dosage determines.It will be understood that the determination of therapeutically effective amount may need trial and error, and may need to adjust dosage And/or dosage regimen.Such treatment optimization and adjustment are covered by the method covered herein.

The term " pharmaceutically acceptable " such as used herein with respect to compound or composition refers to compound or group A kind of form for closing object, can increase or enhance solubility or availability of the compound in subject, to promote or to increase The bioavilability of strong compound or composition.In an aspect, this disclosure also covers the chemical combination embodied herein Pharmaceutically acceptable hydrate, solvate, stereoisomer or the amorphous solid of object and composition.It is pharmaceutically acceptable Composition also refer to can by supervisor government organs approval composition, the supervisor government organs be responsible for approval its administer model Enclose the drug or therapeutic agent of interior sale.For example, the pharmaceutically acceptable composition in U.S.'s sale will be by U.S.'s food and medicine Object management board (FDA) approval.It is pharmaceutically acceptable for the composition for veterinary application or treatment Animal diseases or situation Composition or preparation refer to the composition or system by approval veterinary drug or animal pharmaceuticals for the supervisor regulatory agency approval of sale Agent.

As used herein, " pharmaceutically acceptable carrier " includes as those of ordinary skill in the art will be known any With all solvents, decentralized medium, coating, surfactant, antioxidant, preservative (such as antibacterial agent, antifungal agent), etc. Penetration enhancer, absorption delaying agent, salt, preservative, drug, drug stabilizing agent, gel, adhesive, excipient, disintegrating agent, lubricant, sweet tea Taste agent, flavoring agent, dyestuff, such similar material and combinations thereof are (see, e.g., Remington's Pharmaceutical Sciences, 1990, be incorporated herein by reference).Unless any routine carrier is incompatible with active constituent or application method, it is no Then consider to be used in pharmaceutical composition.

Unless otherwise stated, being (w/w) herein in regard to percentage listed by the specified ingredients in entire combination object. For example, the composition of the DMSO comprising 0.25% PVP-I and 44% has by weight 0.25% relative to total composition PVP-I and by weight 44% DMSO.

In one embodiment, composition includes the iodophor in the range of about 0.01% to about 0.5%, such as PVP-I.In another embodiment, composition includes the iodophor between 0.05% and 0.45%.Another In one embodiment, composition includes the iodophor between 0.1% and 0.3%.In another embodiment In, composition includes the iodophor between 0.15% and 0.25%.In another embodiment, composition packet The iodophor being contained between 0.2% and 0.25%.In another embodiment, composition includes 0.25% iodine Carrier.

In one embodiment, composition includes the PVP-I in the range of about 0.01% to about 0.5%.Another In a embodiment, composition includes the PVP-I between 0.05% and 0.45%.In another embodiment In, composition includes the PVP-I between 0.1% and 0.4%.In another embodiment, composition includes PVP-I between 0.15% and 0.3%.In another embodiment, composition is included in 0.2% He PVP-I between 0.3%.In another embodiment, composition includes between 0.20% and 0.25% PVP-I in range.In another embodiment, composition includes 0.25% PVP-I.

In one embodiment, anhydrous DMSO is used in the composition.In one embodiment, make in the composition With substantially anhydrous DMSO.It will be understood by those skilled in the art that different grades of DMSO can be produced and/or obtain, and A variable in different grades of DMSO product is water content.For example, DMSO can be completely it is anhydrous (also simple herein Referred to as " anhydrous "), it is substantially anhydrous, or the water of measurable degree can be contained.It will be understood that measurable water in DMSO product Amount can be changed based on the limitation for carrying out such instrument measured and technology.In one embodiment, non-complete Complete anhydrous DMSO can be water substantially anhydrous and containing the level lower than detectable level.In an embodiment In, non-fully anhydrous DMSO can contain water, wherein water content be about at least 0.01%, about at least 0.02%, about at least 0.03%, about at least 0.04%, about at least 0.05%, about at least 0.06%, about at least 0.07%, about at least 0.08%, about extremely Few 0.09%, about at least 0.1%, about at least 0.2%, about at least 0.3%, about at least 0.4%, about at least 0.5%, about at least 0.6%, about at least 0.7%, about at least 0.8%, about at least 0.9%, about at least 1.0%, about at least 1.5%, about at least 2.0%, about at least 2.5%, about at least 5%, about at least 7.5%, about at least 10%, about at least 12.5% or bigger.At one In embodiment, non-fully anhydrous DMSO can contain water, wherein water content be approximately less than 0.01%, be approximately less than 0.02%, It is approximately less than 0.03%, 0.04% is approximately less than, is approximately less than 0.05%, is approximately less than 0.06%, is approximately less than 0.07%, is approximately less than 0.08%, it is approximately less than 0.09%, 0.1% is approximately less than, is approximately less than 0.2%, is approximately less than 0.3%, is approximately less than 0.4%, is approximately less than 0.5%, it is approximately less than 0.6%, 0.7% is approximately less than, is approximately less than 0.8%, is approximately less than 0.9%, is approximately less than 1.0%, is approximately less than 1.5%, be approximately less than 2.0%, be approximately less than 2.5%, be approximately less than 5%, be approximately less than 7.5%, be approximately less than 10%, be approximately less than 12.5% or It is bigger.It will be understood that in addition to water, DMSO can contain one or more of other impurities.

In one embodiment, composition includes the United States Pharmacopeia committee (USP) grade DMSO, active pharmaceutical ingredient (API) at least one of grade DMSO, analysis level DMSO and American Chemical Society (ACS) spectrophotometric grade DMSO.In a reality It applies in scheme, composition includes by KF titration with<0.1% water and be determined as on the anhydrous basis>99.9% DMSO。

In one embodiment, composition includes the DMSO in the range of 25% to 99.99%.In an embodiment party In case, composition includes the DMSO being greater than in the range of 25% to 99.99%.In another embodiment, composition packet The DMSO being contained in the range of 30% and 99.9%.In another embodiment, composition, which is included in, is greater than 30% He DMSO in the range of 99.9%.In another embodiment, composition includes in the range of 33% and 99.9% DMSO.In another embodiment, composition includes the DMSO in the range of 35% and 99.9%.In another embodiment party In case, composition includes the DMSO in the range of 40% and 99.9%.In another embodiment, composition is included in DMSO in the range of 50% and 99.9%.In another embodiment, composition is included in the range of 30% and 90% DMSO.In another embodiment, composition includes the DMSO in the range of 35% and 75%.In another embodiment party In case, composition includes the DMSO in the range of 40% and 60%, and in 40% He in another embodiment again DMSO between 50%.In one embodiment, composition includes the DMSO of about 44% weight percent.Implement at one In scheme, composition includes the DMSO of 44% weight percent.

In one embodiment, composition includes DMSO but does not include any other solvent (such as cosolvent) or seep Saturating agent.In another embodiment, composition includes the DMSO in the range of about 30% to 99.99%, and also includes At least one cosolvent in the range of 0.01% to about 70%.In one embodiment, composition includes DMSO, and It also include at least one cosolvent in the range of about 0.1% to about 50%.In an aspect, water is cosolvent.One In a embodiment, composition includes DMSO, water and at least one other cosolvent.

Stability --- it is measured as remaining iodine percentage

In one embodiment, preparation continues at least six moon, 12 months, 18 months and 24 in 25 DEG C of stabilizations of room temperature Month.Stability is defined as, final PVP-I concentration be label concentration at least 85% (for example, if label be to provide 0.2% The 2%PVP-I of iodine, therefore 90% will be 0.18 elemental iodine).

In one embodiment, preparation continues at least six moon, 12 months, 18 months and 24 in 2 DEG C of -8 DEG C of stabilizations of room temperature A month.Stability is defined as, final PVP-I concentration be label concentration at least 90% (for example, if label be to provide The 2%PVP-I of 0.2% iodine, therefore 90% will be 0.18 elemental iodine).

In one embodiment, preparation continues at least six moon, 12 months, 18 months in -10 DEG C of -25 DEG C of stabilizations of room temperature With 24 months.Stability is defined as, final PVP-I concentration be label concentration at least 90% (for example, if label be to provide The 2%PVP-I of 0.2% iodine, therefore 90% will be 0.18 elemental iodine).

In one embodiment, preparation 15 DEG C of -30 DEG C of stabilizations of room temperature continue at least six moon, 12 months, 18 months and 24 months.Stability is defined as, final PVP-I concentration be label concentration at least 90% (for example, if label be to provide The 2%PVP-I of 0.2% iodine, therefore 90% will be 0.18 elemental iodine).

In one embodiment, preparation 40 DEG C of stabilizations of room temperature continue at least one moon, 3 months, 6 months, 12 months, 18 months and 24 months.Stability is defined as, final PVP-I concentration be label concentration at least 90% (for example, if label It is to provide the 2%PVP-I of 0.2% iodine, therefore 90% will be 0.18 elemental iodine).

Preparation method and purposes

It is known to those skilled in the art that PVP-I aqueous solution is difficult to stablize in long period in low PVP-I concentration.Make For non-limiting example, when the concentration of PVP-I is less than about 0.7% (w/w, aqueous solution), PVP-I aqueous solution decays rapidly To generate iodate ingredient and the complex mixture without iodine ingredient.As described herein, it has therefore been surprisingly found that described herein The non-proton DMSO dicyandiamide solution covered of disclosure in, can easily prepare down to 0.1% PVP-I solution and by its Long period is kept as composition is stablized.Same as described herein, the hydration DMSO solution prepared by aqueous PVP-I shows Increased stability, as prompted in for PVP-I component.

In one embodiment, composition includes dry, solid or powdered PVP-I, is dissolved or suspended in In the composition formed comprising DMSO or by DMSO.In another embodiment, DMSO be added into comprising PVP-I or by In the water-based product of PVP-I composition.Based on this disclosure, it will be appreciated by those skilled in the art that how to prepare composition with Obtain iodine, iodophor and the DMSO of desired amount and other the possible components for the composition covered herein.

As non-limiting examples, effective drug is treated using the solid PVP-I preparation being dissolved or suspended in DMSO Composition.In an aspect, composition is anhydrous.In an aspect, composition is substantially anhydrous.At another In embodiment, DMSO may be added in the aqueous solution of PVP-I and treat drug composition effective with preparation.At one In embodiment, DMSO is used as the cosolvent with water with the range of 50%-99%.In one embodiment, preparation packet Containing one or more of excipient.As non-limiting examples, excipient includes but is not limited to sodium chloride, one water of sodium dihydrogen phosphate Close object, Anhydrous Disodium Phosphate and water and other excipient well known by persons skilled in the art.

In one embodiment, by the way that 0.25% PVP-I (w/v, aqueous solution) is added to suitable (q.s.) Composition is prepared in pure DMSO to generate the acquired solution of the 0.25%PVP-I (w/w) with DMSO.In another embodiment party In case, by by solid PVP-I be dissolved in suitable pure DMSO using obtain with DMSO as solvent 0.1%, 0.15%, 0.2%, in 0.25%, 0.3%, 0.35%, 0.4%, 0.45% or 0.5% PVP-I (w/w) it is any come prepare combination Object.In another embodiment again, obtained by the way that solid PVP-I to be dissolved in suitable pure DMSO it is described herein, It describes and/or any composition that covers prepares composition.Comprising aqueous PVP-I (with and without it is commonly used in the art and/ Or known excipient) and the analogous composition of DMSO can be prepared by the aqueous stock solution of 10%PVP-I and pure DMSO.However, It will be understood by those skilled in the art that can make when carrying out dilution and adjusting appropriate to generate desired final PVP-I concentration With any solid or the starting composition of the PVP-I of liquid.

In one embodiment, the case where FHV infection, is especially useful that, it can be in pure USP grades of DMSO solvent Middle stable anhydrous composition of the preparation containing the PVP-I between 0.01%-0.25%.

Based on disclosure set forth herein, it should be understood that in view of the technology of this field, the compound covered herein and The specific dosage of composition can be empirically determined by clinical and/or pharmacokinetics experiment, and such dosage can To be adjusted according to prespecified validity and/or toxicity criterion.It is also understood that any particular patient specific dosage and Therapeutic scheme will depend on various factors, and the feature of activity, patient including used particular compound, is controlled pharmaceutical composition Treat the judgement of doctor and the property and severity of the specified disease treated or situation.For example, the administration of gel preparation includes About 1/2 inch of band is applied directly to ocular surface once or twice daily, preferably under eyelid, until infection is being faced Subside on bed.The administration of liquid preparation includes by 1-5 drop, and typically 2-3 drop composition is applied directly to eyes.

In one embodiment, it includes applying described herein, description that treatment, which has the method for the subject of FHV infection, And/or the composition covered is to treat FHV infection, and progress, prevention of the treatment of FHV infection including preventing or slowing down infection At least some infection and elimination all at least one of infection are eradicated in the diffusion of infection.

In one embodiment, therapeutic composition is administered with scheme once a day.In one embodiment, Therapeutic composition is administered twice daily.In one embodiment, therapeutic composition is three times a day, four times per day, often It it five times or is administered more times daily.In one embodiment, therapeutic composition is to be less than frequency quilt once a day Application.In one embodiment, therapeutic composition once every two days, once every three days, once every four days, it is five days one every It is secondary, once every six days or every seven days are once administered.In one embodiment, therapeutic composition is to be less than once a week Frequency be administered.In one embodiment, therapeutic composition is monthly administered.In one embodiment, it controls The property treated composition is monthly administered twice.

In one embodiment, therapeutic dosing schedule continue at least one day, at least two days, at least three days, extremely It is four days, at least five days, at least six days or at least seven days few.In one embodiment, therapeutic dosing schedule continue for Few one week, at least two weeks, at least three weeks, at least surrounding, at least six weeks, at least eight weeks, at least ten weeks, at least 12 weeks, at least Ten surroundings or at least 16 weeks.In one embodiment, therapeutic dosing schedule continues at least one moon, at least two A month, at least three months, at least four months, at least five months, at least six months, at least nine months or at least 12 months.

The present invention is further described by following embodiment.In an aspect, following embodiment uses present disclosure The composition and method covered demonstrate effective and/or successful treatment to shown situation.It should be appreciated that being based on this hair The variation of bright feature is in the limit of power of those of ordinary skill, and the scope of the present invention should not be limited by example. In order to correctly determine the scope of the present invention, related side is considered as the claims hereof and its any equivalent.In addition, this All documents of text are incorporated by reference into, and unless expressly stated otherwise, otherwise all percentages are by weight.

The embodiment of cat, dog and horse

Following Prophetic example illustrates to use composition as described herein according to the method for the present invention.It is described The result for the treatment of in the scope of the present invention that is expected and conceiving, and therefore can by execute described method and step come Fully achieve, but this to be still based on the prior art unexpected.

It will be understood by those skilled in the art that change can be made to the exemplary implementation scheme being shown and described above, and Without departing from its extensive concept of the invention.It will be understood, therefore, that this disclosure is not limited to shown or described exemplary reality Scheme is applied, and is intended to cover the modification in the spirit and scope of the present invention defined by claim.For example, exemplary embodiment party The special characteristic of case can be or can not be a part of invention claimed, and the spy of disclosed embodiment Sign can be combined.Unless especially illustrating herein, otherwise term " one (a) ", " one (an) " and " being somebody's turn to do (the) " are not limited to one A element, and should be understood that and mean "at least one".

It should be understood that at least some descriptions of the invention have been simplified, it is relevant to the present invention is clearly understood that concentrate on Element, while for the sake of clarity, it eliminates those skilled in the art will appreciate that also may be constructed a part of the invention Other elements.However, because such element is well known in the art, and because they not necessarily facilitate preferably Understand the present invention, therefore the description to these elements is not provided herein.

In addition, specific sequence of steps is not necessarily to be construed as to power for method is independent of specific sequence of steps The limitation that benefit requires.

It should not be limited to the step of they are executed with the sequence of writing for the claim of method of the invention, and Skilled person can easily appreciate that these steps can change and still within the spirit and scope of the present invention.

Domestic cat shows visible, unilateral or bilateral eye infection.It being diagnosed to be infection is drawn by feline herpetovirus (FHV) After rising, such dosage regimen can be used, wherein the group comprising 0.25%PVP-I and 44%DMSO of about 1/2- inch band The surface of one or two eyes of infection can be applied directly to by closing object, preferably between anterior corneal surface and palpebra inferior. Composition can be administered once a day or twice daily, for about three days periods, up to about one week period.Infection To visibly it subside in two days to about one week.It, can be with using described composition compared with the case where not using composition More preferable effect and faster treatment results are provided for infection (recession of infection).

Advantageously, composition is effective, with no harmful side-effects, and is not stimulated the eyes of animal or calcination Sense.

Domestic cat shows visible unilateral corneal infection.It is by the relevant angle of feline herpetovirus (FHV) being diagnosed to be infection After film ulcer causes, such dosage regimen can be used, wherein that about 1/2- inch band includes 0.25%PVP-I and 44% The composition of DMSO can be applied directly to the surface of one or two eyes of infection, preferably in anterior corneal surface and lower eye Between eyelid.Composition can be administered six times per day continues up to two weeks periods.Infection will visibly disappear in about one week It moves back.Compared with the case where not using composition, it can be provided using described composition for infection (recession of infection) more preferable The effect of and faster treatment results.

Domestic cat shows visible, unilateral or bilateral keratoconjunctivitis sicca.It is by feline herpesvirus disease being diagnosed to be infection After malicious (FHV) causes, such dosage regimen can be used, wherein about 1/2- inch band comprising 0.25%PVP-I and The composition of 44%DMSO can be applied directly to the surface of one or two eyes of infection, preferably in anterior corneal surface and Between palpebra inferior.Composition can be administered once a day or twice daily, for about one week period, up to one month Period.Inflammation will visibly subside in a Zhou Zhiyue mono- month.Compared with the case where not using composition, using described Composition more preferable effect and faster treatment results can be provided for inflammation (recession of inflammation).

The cornea of domestic cat shows visible, unilateral immovable black lesion.It is by feline herpesvirus being diagnosed to be lump After viral (FHV) relevant cornea separation causes, such dosage regimen can be used, wherein about 1/2- inch band includes The composition of 0.25%PVP-I and 44%DMSO can be applied directly to the surface of one or two eyes of infection, preferably Ground is between anterior corneal surface and palpebra inferior.Composition can be administered four times per day continues up to two weeks periods.Lump will Visibly subside in about one week.Compared with the case where not using composition, using described composition can for lump or It infects (lump or the recession of infection) and more preferable effect and faster treatment results is provided.

Domestic cat shows uncomfortable visible unilateral eyes, pain and secretion.Fluorescent staining is used in ophthalmoscopy announcement Cornea dendriform ulcer.Patient receives the diagnosis of feline herpetovirus (FHV) epithelial keratitis, and uses such administration Scheme, wherein the composition comprising 0.25%PVP-I and 44%DMSO of about 1/2- inch band is applied directly to infection Ocular surface, preferably between anterior corneal surface and palpebra inferior.The composition daily administration four times, continue ten days.In treatment three After it, dendritic ulcer starts re-epithelialization, and the Corneal inflammation of any surrounding mitigates.Such as demonstrate,proved by normal examination of eyes Real, infection is cured completely in 5 days, and patient restores normally performed activity and activity.

Domestic cat shows visible bilateral eyes discomfort, pain, rubescent and secretion.Ophthalmoscopy discloses bilateral conjunctiva Erythema, with slight chemosis and secretion.Patient receives the diagnosis of the related conjunctivitis of feline herpetovirus (FHV), and Using such dosage regimen, wherein the composition comprising 0.25%PVP-I and 44%DMSO of about 1/2- inch band is straight The ocular surface for being applied to infection is connect, preferably between anterior corneal surface and palpebra inferior.Composition is administered four times per day, is continued Ten days periods.After treatment three days, both chemosis and erythema start to improve.By the 5th day, remaining inflammation subtracted Gently, and eyes examination of eyes is not significant.Patient continues to take out ten days overall processes of sustained drug at place, to prevent spreading Elsewhere into padding (litter).

After with the related conjunctivitis of topical antiviral drug therapy feline herpetovirus (FHV), domestic cat shows visible double Branch hole eyeball discomfort, pain, rubescent and secretion.Ophthalmoscopy discloses bilateral conjunctival erythema, with moderate chemosis and Greenization purulent secretion.After the related conjunctivitis for the treatment of feline herpetovirus (FHV), patient receives related to bacterial overgrowth Bacterial conjunctivitis diagnosis.For treatment, using such dosage regimen, wherein about 1/2- inch band includes The composition of 0.25%PVP-I and 44%DMSO is applied directly to the ocular surface of infection, preferably in anterior corneal surface under Between eyelid.Composition is administered four times per day, continues seven days periods.After treatment three days, suppuration sexual secretion is Resolution, however tie membranous inflammation and persistently exist.By the 5th day, conjunctiva was apparent from, and without chemosis or erythema, and was remained Remaining examination of eyes is not also significant.Patient continues to take out ten days overall processes of sustained drug at place, to prevent from diffusing to pad Expect in (litter) elsewhere.

Domestic cat shows uncomfortable visible unilateral eyes, pain and erythema.Ophthalmoscopy discloses slight conjunctivitis and complete Whole corneal epithelium.In corneal stroma, plate-like infiltration object is presented together with endothelial pellet.Patient receives feline herpetovirus (FHV) diagnosis of related stromal keratitis, and such dosage regimen is used, wherein about 1/2- inch band includes The composition of 0.25%PVP-I and 44%DMSO is applied directly to the ocular surface of infection, preferably in anterior corneal surface under Between eyelid.Composition is administered four times per day, continues two weeks periods.After treatment five days, matrix infiltrates object in density On start to reduce.There is no the signs of breakthrough epithelial keratitis.After ten days, infiltration object continues to reduce, and endothelium becomes Change and conjunctivitis has solved.As confirmed by normal examination of eyes, infection is cured completely in two weeks, and patient is extensive Multiple normally performed activity and activity.

Domestic cat shows uncomfortable visible unilateral eyes, pain and photophobia.Ophthalmoscopy discloses complete cornea and light It is rubescent to spend corneal limbus.Anterior chamber, which checks, discloses 2+ cell and the flash of light without empyesis.Patient receives feline herpetovirus (FHV) phase Close the diagnosis of uveitis, and use such dosage regimen, wherein about 1/2- inch band comprising 0.25%PVP-I and The composition of 44%DMSO is applied directly to the ocular surface of infection, preferably between anterior corneal surface and palpebra inferior.Combination Object is administered six times per day, continues ten days periods.It is treating two days later, anterior chamber's cell and light break reaction are reduced to 1+, and And the photophobia of patient mitigates.Therefore, composition is administered in a manner of gradually decreasing now, and one was used only daily until the tenth day It is secondary.Clearly cornea, white conjunctiva and not only deep but also quiet anterior chamber are disclosed in the inspection of the last day for the treatment of.Patient restores just Normal behavior and activity.

Domestic cat shows uncomfortable visible unilateral eyes, pain and secretion after being hit eyes by branch.Ophthalmoscope inspection Announcement ulcer of the cornea is looked into, there is the knuckle-tooth featheriness edge for being measured as 2x2mm.Be appended corneal infiltration object there is also.Anterior chamber discloses 1 + cell and flash of light.Patient receives the diagnosis of fungal keratitis, and uses such dosage regimen, wherein about 1/2- inches The composition comprising 0.25%PVP-I and 44%DMSO of band is applied directly to the ocular surface of infection, preferably at angle Between film surface and palpebra inferior.Composition is administered four times per day, continues one month period.In after one week treatment, ulcer Start re-epithelialization, size reduces and the Corneal inflammation of any surrounding mitigates.As confirmed by normal examination of eyes, sense Dye is cured completely in three weeks, and patient restores normally performed activity and activity.

Domestic cat shows visible unilateral eyes discomfort at birth, cannot open eyes, pain, rubescent and secretion. Ophthalmoscopy discloses conjunctiva inflammation with the punctate epithelial errosions of moderate chemosis and anterior corneal surface.There is also mucus purulence Sexual secretion.Patient receives the diagnosis of feline herpetovirus (FHV) associated neogenesis ophthalmia.Therefore, using such dosage regimen, Wherein the composition comprising 0.25%PVP-I and 44%DMSO of about 1/2- inch band is applied directly to the eyes table of infection Face, preferably between anterior corneal surface and palpebra inferior.Composition is administered four times per day, continues one week period.It is treating Two days later, kitten can independently open eyes.After treatment five days, secretion has stopped, and conjunctiva inflammation is significant Improve.As confirmed by normal examination of eyes, infection is cured completely in seven days, and patient returns to padding, shows Normally performed activity and activity.

Domestic cat shows uncomfortable visible unilateral eyes, pain and the erythema with secretion.It is impacted when visual inspection Eyes there is pink/grey.Ophthalmoscopy discloses slight conjunctivitis and complete corneal epithelium, however, periphery cornea Edge discloses the Boss with infiltration of micro corneal limbus week object.Patient receives the related acidophilia cornea of feline herpetovirus (FHV) Scorching diagnosis, and such dosage regimen is used, wherein that about 1/2- inch band includes 0.25%PVP-I and 44%DMSO Composition be applied directly to the ocular surface of infection, preferably between anterior corneal surface and palpebra inferior.Composition daily four It is secondary to be administered, continue two weeks periods.After treatment five days, corneal limbus infiltration object in periphery starts to reduce in density.It does not deposit In the sign of breakthrough epithelial keratitis.After ten days, infiltration object continues to reduce, and conjunctivitis has solved.Such as pass through What normal examination of eyes and color confirmed, infection is cured completely in two weeks.Patient restores normally performed activity and activity.

By showing uncomfortable visible unilateral eyes, pain and secretion after wound when domestic cat is at play.Ophthalmoscope inspection It looks into and discloses suppurative ulcer of the cornea, there is the 30% matrix loss for being measured as 3x3mm.Anterior chamber discloses 1+ cell and flash of light, but right Empyesis is negative.Patient receives the diagnosis of the relevant bacterila corneal ulcer of wound, and uses such administration Scheme, wherein the composition comprising 0.25%PVP-I and 44%DMSO of about 1/2- inch band is applied directly to infection Ocular surface, preferably between anterior corneal surface and palpebra inferior.Composition is administered four times per day, continues one month time Section.In after one week treatment, ulcer starts re-epithelialization, and size reduces and the Corneal inflammation of any surrounding mitigates.Such as by just What normal examination of eyes confirmed, infection is cured completely in three weeks, and patient restores normally performed activity and activity.

Domestic cat shows visible bilateral eyes discomfort, pain, rubescent and secretion after the cat infected with other contacts. Ophthalmoscopy discloses bilateral conjunctival erythema, with moderate chemosis and secretion.Patient receives Chlamydia or mycoplasma The diagnosis of related conjunctivitis, and use such dosage regimen, wherein about 1/2- inch band comprising 0.25%PVP-I and The composition of 44%DMSO is applied directly to the ocular surface of infection, preferably between anterior corneal surface and palpebra inferior.Combination Object is administered twice daily, continues one week period.After treatment three days, both chemosis and erythema start to improve. By the 5th day, remaining inflammation mitigated, and eyes examination of eyes is not significant.Patient continues to take out sustained drug seven days of place Overall process, so as to prevent from diffusing to cattery elsewhere.

Domesticated dog shows uncomfortable visible unilateral eyes, pain and secretion.Fluorescent staining is used in ophthalmoscopy announcement Cornea dendriform ulcer.Patient receives the diagnosis of canine alphaherpesvirus (CHV) epithelial keratitis, and uses such administration Scheme, wherein the composition comprising 0.25%PVP-I and 44%DMSO of about 1/2- inch band is applied directly to infection Ocular surface, preferably between anterior corneal surface and palpebra inferior.Composition is administered four times per day, continues ten days periods. After treatment three days, dendritic ulcer starts re-epithelialization, and the Corneal inflammation of any surrounding mitigates.Such as pass through normal eye Portion checks that confirmation, infection are cured completely in 5 days, and patient restores normally performed activity and activity.

Domesticated dog shows uncomfortable visible unilateral eyes, pain and secretion after being hit eyes by vegetable matter.Inspection Ophthalmoscopy discloses ulcer of the cornea, has the knuckle-tooth featheriness edge for being measured as 2x2mm.Be appended corneal infiltration object there is also.Before Disclose 1+ cell and flash of light in room.Patient receives the diagnosis of fungal keratitis, and uses such dosage regimen, wherein about 1/ The composition comprising 0.25%PVP-I and 44%DMSO of 2- inch band is applied directly to the ocular surface of infection, preferably Ground is between anterior corneal surface and palpebra inferior.Composition is administered four times per day, continues one month period.In one week treatment Afterwards, ulcer starts re-epithelialization, and size reduces and the Corneal inflammation of any surrounding mitigates.Such as demonstrate,proved by normal examination of eyes Real, infection is cured completely in three weeks, and patient restores normally performed activity and activity.

After with the related conjunctivitis of topical antiviral drug therapy canine alphaherpesvirus (CHV), domesticated dog shows visible double Branch hole eyeball discomfort, pain, rubescent and secretion.Ophthalmoscopy discloses bilateral conjunctival erythema, with moderate chemosis and Greenization purulent secretion.After the related conjunctivitis for the treatment of canine alphaherpesvirus (CHV), patient receives related to bacterial overgrowth Bacterial conjunctivitis diagnosis.For treatment, using such dosage regimen, wherein about 1/2- inch band includes The composition of 0.25%PVP-I and 44%DMSO is applied directly to the ocular surface of infection, preferably in anterior corneal surface under Between eyelid.Composition is administered four times per day, continues seven days periods.After treatment three days, suppuration sexual secretion is Resolution, however tie membranous inflammation and persistently exist.By the 5th day, conjunctiva was apparent from, and without chemosis or erythema, and was remained Remaining examination of eyes is not also significant.Patient continues to take out ten days overall processes of sustained drug at place, feeding to prevent from diffusing to At dog elsewhere.

Domesticated dog shows visible unilateral eyes and does not accommodate eyelid scratch (excoriation).Ophthalmoscopy discloses strong The conjunctiva inspection of health and cornea without ulcer.Eyelid inspection discloses the aphtha at eyelid, with eyelid oedema, red Spot, eyelashes pad and dandruff.Patient receives the diagnosis of the related blepharitis of canine alphaherpesvirus (CHV), and gives prescription using such Case, wherein the composition comprising 0.25%PVP-I and 44%DMSO of about 1/2- inch band is applied directly to the eye of infection Eyeball surface, preferably between anterior corneal surface and palpebra inferior.Composition is administered four times per day, continues two weeks periods.? After treatment three days, lid ulcer starts re-epithelialization, and the lid inflammation of surrounding mitigates.As by eyelid and eyelashes inflammation What normal examination of eyes and resolution ratio confirmed, infection is cured completely in two weeks.Patient restores normally performed activity and activity.

Domesticated dog shows visible bilateral eyes discomfort, pain, rubescent and secretion.Ophthalmoscopy discloses bilateral conjunctiva Erythema, with slight chemosis and secretion.Patient receives the diagnosis of the related conjunctivitis of canine alphaherpesvirus (CHV), and Using such dosage regimen, wherein the composition comprising 0.25%PVP-I and 44%DMSO of about 1/2- inch band is straight The ocular surface for being applied to infection is connect, preferably between anterior corneal surface and palpebra inferior.Composition is administered four times per day, is continued Ten days periods.After treatment three days, both chemosis and erythema start to improve.By the 5th day, remaining inflammation subtracted Gently, and eyes examination of eyes is not significant.Patient continues to take out ten days overall processes of sustained drug at place, to prevent spreading Elsewhere into padding.

Domesticated dog shows visible bilateral eyes discomfort, pain, rubescent and secretion after the dog infected with other contacts. Ophthalmoscopy discloses bilateral conjunctival erythema, with moderate chemosis and secretion.Patient receives bacterial conjunctivitis Diagnosis, and such dosage regimen is used, wherein the group comprising 0.25%PVP-I and 44%DMSO of about 1/2- inch band The ocular surface that object is applied directly to infection is closed, preferably between anterior corneal surface and palpebra inferior.Composition twice daily by Application, continues one week period.After treatment three days, both chemosis and erythema start to improve.By the 5th day, residual Inflammation mitigate, and eyes examination of eyes is not significant.Patient continues to take out seven days overall processes of sustained drug at place, so as to It prevents from diffusing at feeding dog elsewhere.

Domesticated dog shows visible bilateral eye erythema and slight mucus secretion.It is rotten that ophthalmoscopy discloses dotted cornea The tear rupture time of rotten, slight conjunctivitis and reduction.Patient receives the related keratoconjunctivitis sicca of canine alphaherpesvirus (CHV) Diagnosis, and use such dosage regimen, wherein about 1/2- inch band comprising 0.25%PVP-I and 44%DMSO Composition can be applied directly to the surface of the one or two eyes of infection, preferably in anterior corneal surface and palpebra inferior Between.Composition is administered twice daily, for about one week period, up to one month period.In after one week treatment, Inflammation starts visibly to subside, as confirmed by improved tear rupture time.After 3 weeks, conjunctival erythema is cleared up, and is remained Remaining examination of eyes is in the normal range.Patient restores normally performed activity and activity.

Domesticated dog shows uncomfortable visible unilateral eyes, pain and clearly secretion.Ophthalmoscopy discloses slight knot Film injection and diffusivity, punctate epithelial errosions are present in anterior corneal surface.Anterior chamber is not only deep but also quiet.Patient receives canine alphaherpesvirus (CHV) diagnosis of non-ulcerative keratitis, and such dosage regimen is used, wherein about 1/2- inch band includes The composition of 0.25%PVP-I and 44%DMSO is applied directly to the ocular surface of infection, preferably in anterior corneal surface under Between eyelid.Composition is administered four times per day, continues ten days periods.After treatment three days, corneal eptithelial detachment starts to cure, And the Corneal inflammation around any mitigates.As confirmed by normal examination of eyes, infection is cured completely in 5 days, and And patient restores normally performed activity and activity.

By showing uncomfortable visible unilateral eyes, pain and secretion after wound when domesticated dog is at play.Ophthalmoscope inspection It looks into and discloses suppurative ulcer of the cornea, there is the 30% matrix loss for being measured as 3x3mm.Anterior chamber discloses 1+ cell and flash of light, but right Empyesis is negative.Patient receives the diagnosis of the relevant bacterila corneal ulcer of wound, and uses such administration Scheme, wherein the composition comprising 0.25%PVP-I and 44%DMSO of about 1/2- inch band is applied directly to infection Ocular surface, preferably between anterior corneal surface and palpebra inferior.Composition is administered four times per day, continues one month time Section.In after one week treatment, ulcer starts re-epithelialization, and size reduces and the Corneal inflammation of any surrounding mitigates.Such as by just What normal examination of eyes confirmed, infection is cured completely in three weeks, and patient restores normally performed activity and activity.

Domesticated dog shows uncomfortable visible unilateral eyes, pain and the erythema with secretion.It is impacted when visual inspection Eyes there is pink/grey.Ophthalmoscopy discloses slight conjunctivitis and complete corneal epithelium, however, periphery cornea Edge discloses the pink colour or grey tubercle of the protuberance with micro corneal limbus Zhou Baise infiltration object.Patient receives canine alphaherpesvirus (CHV) diagnosis of related eosinophilic keratitis, and such dosage regimen is used, wherein about 1/2- inch band includes The composition of 0.25%PVP-I and 44%DMSO is applied directly to the ocular surface of infection, preferably in anterior corneal surface under Between eyelid.Composition is administered four times per day, continues two weeks periods.After treatment five days, periphery corneal limbus infiltrates object Start to reduce in density.There is no the signs of breakthrough epithelial keratitis.After ten days, infiltration object continues to reduce, and Conjunctivitis has solved.As confirmed by normal examination of eyes and color, infection is cured completely in two weeks.Patient restores Normally performed activity and activity.

Thoroughbred racehorses showed after the horse infected with other contacts visible bilateral eyes discomfort, pain, it is rubescent and point Secretion.Ophthalmoscopy discloses bilateral conjunctival erythema, with moderate chemosis and clearly secretion.In the presence of a small amount of dyeing Punctate epithelial errosions.Patient receives the diagnosis of horse herpes virus (EHV) related popularity keratoconjunctivitis, and uses this The dosage regimen of sample, wherein the composition comprising 0.25%PVP-I and 44%DMSO of about 1/2- inch band is directly applied To the ocular surface of infection, preferably between anterior corneal surface and palpebra inferior.Composition is administered twice daily, continues two weeks Period.After treatment three days, both chemosis and erythema start to improve.By the 5th day, remaining inflammation mitigated, and Eyes examination of eyes is not significant.Patient continues to take out seven days overall processes of sustained drug at place, to prevent diffusing to other Place.

Family horse shows visible bilateral eyes discomfort, pain, rubescent and secretion.Ophthalmoscopy discloses bilateral conjunctiva Erythema, with moderate chemosis and clearly secretion.In the presence of a small amount of dyeing punctate epithelial errosions.Patient receives horse The diagnosis of herpesviral (EHV) correlation keratoconjunctivitis, and such dosage regimen is used, wherein about 1/2- inch band Composition comprising 0.25%PVP-I and 44%DMSO is applied directly to the ocular surface of infection, preferably in anterior corneal surface Between palpebra inferior.Composition is administered twice daily, continues two weeks periods.Treatment three days after, chemosis and Both erythema start to improve.By the 5th day, remaining inflammation mitigated, and eyes examination of eyes is not significant.Patient continues to take Seven days overall processes of sustained drug at place are opened, to reduce virus shedding.

Thoroughbred racehorses show uncomfortable visible unilateral eyes, pain and the erythema with secretion.When visual inspection, by There is pink/grey in the eyes of influence.Ophthalmoscopy discloses slight conjunctivitis and complete corneal epithelium, however, periphery Corneal limbus discloses the pink colour or grey tubercle of the protuberance with micro corneal limbus Zhou Baise infiltration object.Patient receives horse herpes virus (EHV) diagnosis of related eosinophilic keratitis, and such dosage regimen is used, wherein about 1/2- inch band includes The composition of 0.25%PVP-I and 44%DMSO is applied directly to the ocular surface of infection, preferably in anterior corneal surface under Between eyelid.Composition is administered four times per day, continues two weeks periods.After treatment five days, periphery corneal limbus infiltrates object Start to reduce in density.There is no the signs of breakthrough epithelial keratitis.After ten days, infiltration object continues to reduce, and Conjunctivitis has solved.As confirmed by normal examination of eyes and color, infection is cured completely in two weeks.Patient restores Normally performed activity and activity.

Thoroughbred racehorses show loss of appetite and left vision function reduction.When visual inspection, eyes and attachment appearance are just Often.Ophthalmoscopy discloses normal leading portion；However, dynamic retinoscopy, which discloses multifocal chorioretinal, infiltrates object.Patient Receive the diagnosis of the related multifocal choroidoretinitis of horse herpes virus (EHV), and uses such dosage regimen, wherein The composition comprising 0.25%PVP-I and 44%DMSO of about 1/2- inch band is applied directly to the ocular surface of infection, Preferably between anterior corneal surface and palpebra inferior.Composition is administered four times per day, continues two weeks periods.After a week, Multifocal lesion starts to clear up, and it is parallel normal that patient, which starts feed,.Such as commented by normal examination of eyes and retina Estimate confirmation, infection is cured completely in two weeks.Patient continues normally performed activity and activity.

Family horse shows uncomfortable visible unilateral eyes, pain and secretion.Fluorescent staining is used in ophthalmoscopy announcement Cornea dendriform ulcer.Patient receives the diagnosis of horse herpes virus (EHV) epithelial keratitis, and uses such administration Scheme, wherein the composition comprising 0.25%PVP-I and 44%DMSO of about 1/2- inch band is applied directly to infection Ocular surface, preferably between anterior corneal surface and palpebra inferior.Composition is administered four times per day, continues ten days periods. After treatment three days, dendritic ulcer starts re-epithelialization, and the Corneal inflammation of any surrounding mitigates.Such as pass through normal eye Portion checks that confirmation, infection are cured completely in 5 days, and patient restores normally performed activity and activity.

Thoroughbred racehorses show uncomfortable visible unilateral eyes, pain and secretion after being hit eyes by branch.Examine eye Spectroscopy discloses ulcer of the cornea, has the knuckle-tooth featheriness edge for being measured as 2x2mm.Be appended corneal infiltration object there is also.Anterior chamber Disclose 1+ cell and flash of light.Patient receives the diagnosis of mycotic corneal ulcer, and uses such dosage regimen, wherein about 1/ The composition comprising 0.25%PVP-I and 44%DMSO of 2- inch band is applied directly to the ocular surface of infection, preferably Ground is between anterior corneal surface and palpebra inferior.Composition is administered four times per day, continues one month period.In one week treatment Afterwards, ulcer starts re-epithelialization, and size reduces and the Corneal inflammation of any surrounding mitigates.Such as demonstrate,proved by normal examination of eyes Real, infection is cured completely in three weeks, and patient restores normally performed activity and activity.

By showing uncomfortable visible unilateral eyes, pain and secretion after wound when thoroughbred racehorses are at play.Examine eye Spectroscopy discloses suppurative ulcer of the cornea, has the 30% matrix loss for being measured as 3x3mm.Anterior chamber discloses 1+ cell and flash of light, It but is negative to empyesis.Patient receives the diagnosis of the relevant bacterila corneal ulcer of wound, and as use Dosage regimen, wherein the composition comprising 0.25%PVP-I and 44%DMSO of about 1/2- inch band is applied directly to sense The ocular surface of dye, preferably between anterior corneal surface and palpebra inferior.Composition is administered four times per day, continue one month when Between section.In after one week treatment, ulcer starts re-epithelialization, and size reduces and the Corneal inflammation of any surrounding mitigates.Such as pass through What normal examination of eyes confirmed, infection is cured completely in three weeks, and patient restores normally performed activity and activity.

Family horse shows visible unilateral eyes and does not accommodate eyelid scratch.Ophthalmoscopy disclose health conjunctiva inspection and Cornea without ulcer.Eyelid inspection discloses the aphtha at eyelid, with eyelid oedema, erythema, eyelashes pad and head Scurf.Patient receives the diagnosis of the related blepharitis of horse herpes virus (EHV), and uses such dosage regimen, wherein about 1/2- The composition comprising 0.25%PVP-I and 44%DMSO of inch band is applied directly to the ocular surface of infection, preferably Between anterior corneal surface and palpebra inferior.Composition is administered twice daily, continues two weeks periods.After treatment three days, eye Eyelid ulcer starts re-epithelialization, and the lid inflammation of surrounding mitigates.Such as pass through eyelid and the inspection of the normal eye of eyelashes inflammation Look into resolution ratio confirm, infection cured completely in two weeks.Patient restores normally performed activity and activity.

Family horse shows uncomfortable visible unilateral eyes, pain and clearly secretion.Ophthalmoscopy discloses slight knot Film injection and diffusivity, punctate epithelial errosions are present in anterior corneal surface.Anterior chamber is not only deep but also quiet.Patient receives horse herpes virus (EHV) diagnosis of non-ulcerative keratitis, and such dosage regimen is used, wherein about 1/2- inch band includes The composition of 0.25%PVP-I and 44%DMSO is applied directly to the ocular surface of infection, preferably in anterior corneal surface under Between eyelid.Composition is administered four times per day, continues ten days periods.After treatment three days, corneal eptithelial detachment starts to cure, And the Corneal inflammation around any mitigates.As confirmed by normal examination of eyes, infection is cured completely in 5 days, and And patient restores normally performed activity and activity.

Thoroughbred racehorses show visible bilateral eye erythema and slight mucus secretion.Ophthalmoscopy discloses dotted angle The tear rupture time of film rotten to the corn, slight conjunctivitis and reduction.Patient receives the related drying property cornea knot of horse herpes virus (EHV) The diagnosis of film inflammation, and such dosage regimen is used, wherein that about 1/2- inch band includes 0.25%PVP-I and 44% The composition of DMSO can be applied directly to the surface of the one or two eyes of infection, preferably in anterior corneal surface and Between palpebra inferior.Composition is administered twice daily, for about one week period, up to one month period.It is treating After a week, inflammation starts visibly to subside, as confirmed by improved tear rupture time.After 3 weeks, conjunctival erythema disappears Solution, and remaining examination of eyes is in the normal range.Patient restores normally performed activity and activity.

After with the related conjunctivitis of topical antiviral drug therapy horse herpes virus (EHV), thoroughbred racehorses show visible Bilateral eyes discomfort, pain, rubescent and secretion.Ophthalmoscopy discloses bilateral conjunctival erythema, with moderate chou film water Swollen and greenization purulent secretion.After the related conjunctivitis for the treatment of horse herpes virus (EHV), patient receives and bacterial overgrowth The diagnosis of relevant bacterial conjunctivitis.For treatment, using such dosage regimen, wherein about 1/2- inch band includes The composition of 0.25%PVP-I and 44%DMSO is applied directly to the ocular surface of infection, preferably in anterior corneal surface under Between eyelid.Composition is administered twice daily, continues seven days periods.After treatment three days, suppuration sexual secretion is Resolution, however tie membranous inflammation and persistently exist.By the 5th day, conjunctiva was apparent from, and without chemosis or erythema, and was remained Remaining examination of eyes is not also significant.Patient continues to take out ten days overall processes of sustained drug at place, feeding to prevent from diffusing to At dog elsewhere.

Thoroughbred racehorses show uncomfortable visible unilateral eyes, pain and erythema.Ophthalmoscopy discloses slight conjunctivitis With complete corneal epithelium.In corneal stroma, plate-like infiltration object is presented together with endothelial pellet.Patient receives horse blister sore The diagnosis of malicious (EHV) related stromal keratitis, and such dosage regimen is used, wherein about 1/2- inch band includes The composition of 0.25%PVP-I and 44%DMSO is applied directly to the ocular surface of infection, preferably in anterior corneal surface under Between eyelid.Composition is administered four times per day, continues two weeks periods.After treatment five days, matrix infiltrates object in density On start to reduce.There is no the signs of breakthrough epithelial keratitis.After ten days, infiltration object continues to reduce, and endothelium becomes Change and conjunctivitis has solved.As confirmed by normal examination of eyes, infection is cured completely in two weeks, and patient is extensive Multiple normally performed activity and activity.

Claims (26)

1. a kind of method of the herpesvirus infection in eyes for treating animal, which comprises

Povidone iodine (PVP-I) comprising 0.01% to 5.0% and pharmaceutically acceptable group greater than 30% DMSO are provided Close object；With

A effective amount of composition is applied to the eyes of the animal.

2. the method as described in claim 1, wherein the composition includes 0.25% PVP-I.

3. the method as described in claim 1, wherein the composition includes 44% DMSO.

4. the method as described in claim 1, wherein the composition also includes cosolvent.

5. the method as described in claim 1, wherein the composition includes the amount for being effectively formed stable gel combination Gelling agent.

6. method as claimed in claim 5, wherein the gelling agent is selected from natural gum, agar, carragheen, vaseline and cellulose Polymer.

7. method as claimed in claim 5, wherein the gelling agent is cellulosic polymer.

8. the method for claim 7, wherein the cellulosic polymer is hydroxyethyl cellulose.

9. the method as described in claim 1, wherein the animal is non-human.

10. method as claimed in claim 9, wherein the animal is cat, and the herpesviral is feline herpetovirus (FHV)。

11. method as claimed in claim 9, wherein the animal is dog, and the herpesviral is canine alphaherpesvirus (CHV)。

12. method as claimed in claim 9, wherein the animal is horse, and the herpesviral is horse herpes virus (EHV)。

13. the method as described in claim 1, wherein the herpesvirus infection is herpetic keratitis.

14. a kind of pharmaceutically acceptable composition of the herpesvirus infection in eyes for treating animal, the combination Object includes:

From 0.01% to 5.0% povidone iodine (PVP-I) and the DMSO greater than 30%；

Wherein the composition is administered to the eyes of the animal with effective quantity to improve or eliminate the infection.

15. composition as claimed in claim 14, wherein the composition includes 0.25% PVP-I.

16. composition as claimed in claim 14, wherein the composition includes 44% DMSO.

17. composition as claimed in claim 14, wherein the composition also includes cosolvent.

18. composition as claimed in claim 14, wherein the composition includes to be effectively formed stable gel combination The gelling agent of amount.

19. composition as claimed in claim 18, wherein the gelling agent is selected from natural gum, agar, carragheen, vaseline and fibre Tie up plain polymer.

20. composition as claimed in claim 18, wherein the gelling agent is cellulosic polymer.

21. composition as claimed in claim 20, wherein the cellulosic polymer is hydroxyethyl cellulose.

22. composition as claimed in claim 14, wherein the composition is administered to non-human mammal.

23. composition as claimed in claim 14, wherein the composition is administered to cat, and the herpesviral is cat Herpesviral (FHV).

24. composition as claimed in claim 14, wherein the composition is administered to dog, and the herpesviral is dog Herpesviral (CHV).

25. composition as claimed in claim 14, wherein the composition is administered to horse, and the herpesviral is horse Herpesviral (EHV).

26. composition as claimed in claim 14, wherein the composition is used for herpetic keratitis.